Gene-expression patterns and susceptibility to allergic responses

Expert Review of Clinical Immunology

Volumn 2, Issue 1, 2006, Pages 59-73

  Williams, Marc ^a   Georas, Steve ^a  

^a JOHNS HOPKINS ASTHMA AND ALLERGY CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLERGEN; CD40 LIGAND; CPG OLIGODEOXYNUCLEOTIDE; DOUBLE STRANDED RNA; ENDOTOXIN; FLAGELLIN; GAMMA INTERFERON; GLUCOCORTICOID; IMMUNOGLOBULIN E; INTERFERON RECEPTOR; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 5; INTERLEUKIN 6; LYMPHOCYTE ANTIGEN RECEPTOR; STAT1 PROTEIN; STAT6 PROTEIN; STEROID; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR T BET; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

ALLERGIC DISEASE; ANTIINFLAMMATORY ACTIVITY; ASTHMA; ATOPY; B LYMPHOCYTE; CELL DIFFERENTIATION; CELLULAR IMMUNITY; CHROMATIN ASSEMBLY AND DISASSEMBLY; CYTOKINE PRODUCTION; DENDRITIC CELL; DRUG POTENCY; ENVIRONMENTAL EXPOSURE; GENE EXPRESSION REGULATION; GENETIC SUSCEPTIBILITY; GENETIC TRANSCRIPTION; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; MAJOR HISTOCOMPATIBILITY COMPLEX; MICROENVIRONMENT; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TH1 CELL; TH2 CELL; TH3 CELL;

EID: 33748486025     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/14787210.2.1.59     Document Type: Review

References (180)

1. Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J. Allergy Clin. Immunol. 116, 377-383 (2005).
2. Sampson HA. Clinical practice. Peanut allergy. N. Engl. J. Med. 346, 1294-1299 (2002).
3. Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Ann. Rev. Immunol. 17, 255-281 (1999).
4. Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Ann. Rev. Immunol. 22, 789-815 (2004).
5. Georas SN, Beck LA, Stellato C. What is eotaxin doing in the pleura? Insights into innate immunity from pleural mesothelial cells. Am. J. Respir. Cell Mol. Biol. 26, 384-387 (2002).
6. Vercelli D. Genetic polymorphism in allergy and asthma. Curr. Opin. Immunol. 15, 609-613 (2003).
7. Hoffjan S, Nicolae D, Ober C. Association studies for asthma and atopic diseases: a comprehensive review of the literature. Respir. Res. 4, 14 (2003).
8. Eder W, von Mutius E. Hygiene hypothesis and endotoxin: what is the evidence? Curr. Opin. Allergy Clin. Immunol. 4, 113-117 (2004).
9. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N. Engl. J. Med. 343, 538-543 (2000).
10. Braun-Fahrlander C, Riedler J, Herz U et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl. J. Med. 347, 869-877 (2002).
11. Zutavern A, Hirsch T, Leupold W, Weiland S, Keil U, von Mutius E. Atopic dermatitis, extrinsic atopic dermatitis and the hygiene hypothesis: results from a cross-sectional study. Clin. Exp. Allergy 35, 1301-1308 (2005).
12. Celedon JC, Wright RJ, Litonjua AA et al. Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years. Am. J. Respir. Crit. Care Med. 167, 1239-1243 (2003).
13. Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev. Immunol. 1, 69-75 (2001).
14. Holt PG, Thomas WR. Sensitization to airborne environmental allergens: unresolved issues. Nature Immunol. 6, 957-960 (2005).
15. Robinson D, Hamid Q, Ying S et al. Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-γ cytokine gene expression. Am. Rev. Respir. Dis. 148, 401-406 (1993).
16. Robinson D, Ying S, Bentley A et al. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J. Allergy Clin. Immunol. 92, 397-403 (1993).
17. Robinson DS, Hamid Q, Ying S et al. Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl. J. Med. 326, 298-304 (1992).
18. Leung DY, Martin RJ, Szefler SJ et al. Dysregulation of interleukin-4, interleukin-5, and interferon gamma gene expression in steroid-resistant asthma. J. Exp. Med. 181, 33-40 (1995).
19. Benson M, Strannegard IL, Wennergren G, Strannegard O. Low levels of interferon-γ in nasal fluid accompany raised levels of T-helper 2 cytokines in children with ongoing allergic rhinitis. Pediatr. Allergy Immunol. 11, 20-28 (2000).
20. Lee CH, Rhee CS, Oh SH, Min YG, Lee MS. Increase in expression of IL-4 and IL-5 mRNA in the nasal mucosa of patients with perennial allergic rhinitis during natural allergen exposure. Ann. Otol. Rhinol. Laryngol. 106, 215-219 (1997).
21. Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J. Clin. Invest. 94, 870-876 (1994).
22. Martin RJ, Boguniewicz M, Henson JE et al. The effects of inhaled interferon gamma in normal human airways. Am. Rev. Respir. Dis. 148, 1677-1682 (1993).
23. Randolph DA, Stephens R, Carruthers CJ, Chaplin DD. Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Invest. 104, 1021-1029 (1999).
24. Ford JG, Rennick D, Donaldson DD et al. Il-13 and IFN-γ: interactions in lung inflammation. J. Immunol. 167, 1769-1777 (2001).
25. Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon γ regulate allergic airway inflammation and mucus production. J. Exp. Med. 190, 1309-1318 (1999).
26. + T cells in asthma. Am. J. Respir. Crit. Care Med. 161, 1790-1796 (2000).
27. Heaton T, Rowe J, Turner S et al. An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet 365, 142-149 (2005).
28. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J. Clin. Invest. 113, 651-657 (2004).
29. Thepen T, Langeveld-Wildschut EG, Bihari IC et al. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial Th2 response to a Th1 response in situ: an immunocytochemical study. J. Allergy Clin. Immunol. 97, 828-837 (1996).
30. Ingordo V, Dalle Nogare R, Colecchia B, D'Andria C. Is the atopy patch test with house dust mites specific for atopic dermatitis? Dermatology 209, 276-283 (2004).
31. Wollenberg A, Kraft S, Hanau D, Bieber T. Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J. Invest. Dermatol. 106, 446-453 (1996).
32. Novak N, Valenta R, Bohle B et al. FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J. Allergy Clin. Immunol. 113, 949-957 (2004).
33. de Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, Bihari IC, Bruijnzeel-Koomen CA, Thepen T. Nonspecific T-cell homing during inflammation in atopic dermatitis: expression of cutaneous lymphocyte-associated antigen and integrin αE β7 on skin-infiltrating T cells. J. Allergy Clin. Immunol. 100, 694-701 (1997).
34. Wu C, Fargeas C, Nakajima T, Delespesse G. Glucocorticoids suppress the production of interleukin-4 by human lymphocytes. Eur. J. Immunol. 21, 2645-2647 (1991).
35. Byron K, Varigo G, Wootton A. Hydrocortisone inhibition of human interleukin-4. Immunol. 77, 624-626 (1992).
36. Chikanza LC, Panayi GS. The effects of hydrocortisone on in vitro lymphocyte proliferation and interleukin-2 and -4 production in corticosteroid sensitive and resistant subjects. Eur. J. Clin. Invest. 23, 845-850 (1993).
37. Schmidt J, Fleissner S, Heimann-Weitschat I, Lindstaedt R, Szelenyi I. The effect of different corticosteroids and cyclosporin A on interleukin-4 and interleukin-5 release from murine Th2-type T cells. Eur. J. Pharmacol. 260, 247-250 (1994).
38. Krouwels F, van der Heijden J, Lutter R, van Neervan R, Jansen H, Out T. Glucocorticoids affect functions of airway and blood-derived human T cell clones. Am. J. Respir. Cell Mol. Biol. 14, 388-397 (1996).
39. + T cells. J. Allergy Clin. Immunol. 100, 511-519 (1997).
40. Braun CM, Huang SK, Bashian GG, Kagey-Sobotka A, Lichtenstein LM, Essayan DM. Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses. J. Allergy Clin. Immunol. 100, 400-407 (1997).
41. Naseer T, Minshall EM, Leung DY et al. Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am. J. Respir. Crit. Care Med. 155, 845-851 (1997).
42. Corrigan CJ, Hamid Q, North J et al. Peripheral blood CD4 but not CD8 t-lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-Type pattern: effect of glucocorticoid therapy. Am. J. Respir. Cell Mol. Biol. 12, 567-578 (1995).
43. Majori M, Piccoli ML, Bertacco S, Cuomo A, Cantini L, Pesci A. Inhaled beclomethasone dipropionate downregulates CD4 and CD8 T-lymphocyte activation in peripheral blood of patients with asthma. J. Allergy Clin. Immunol. 100, 379-382 (1997).
44. Gemou-Engesaeth V, Bush A, Kay AB, Hamid Q, Corrigan CJ. Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and 'Th2-type' cytokine mRNA expression. Pediatrics 99, 695-703 (1997).
45. Gemou-Engesaeth V, Fagerhol MK, Toda M et al. Expression of activation markers and cytokine mRNA by peripheral blood CD4 and CD8 T cells in atopic and nonatopic childhood asthma: effect of inhaled glucocorticoid therapy. Pediatrics 109, E24 (2002).
46. Harris NL, Watt V, Ronchese F, Le Gros G. Differential T cell function and fate in lymph node and nonlymphoid tissues. J. Exp. Med. 195, 317-326 (2002).
47. Reinhardt RL, Bullard DC, Weaver CT, Jenkins MK. Preferential accumulation of antigen-specific effector CD4 T cells at an antigen injection site involves CD62E-dependent migration but not local proliferation. J. Exp. Med. 197, 751-762 (2003).
48. Seki N, Miyazaki M, Suzuki W et al. IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation. J. Immunol. 172, 6158-6166 (2004).
49. Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nature Rev. Immunol. 2, 933-944 (2002).
50. Grogan JL, Mohrs M, Harmon B, Lacy DA, Sedat JW, Locksley RM. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14, 205-215 (2001).
51. Eisenbarth SC, Zhadkevich A, Ranney P, Herrick CA, Bottomly K. IL-4-dependent Th2 collateral priming to inhaled antigens independent of toll-like receptor 4 and myeloid differentiation factor 88. J. Immunol. 172, 4527-4534 (2004).
52. Usui T, Nishikomori R, Kitani A, Strober W. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rβ2 chain or T-bet. Immunity 18, 415-428 (2003).
53. Galvao Da Silva AP, Jacysyn JF, De Almeida Abrahamsohn I. Resistant mice lacking interleukin-12 become susceptible to Trypanosoma cruzi infection but fail to mount a T helper Type 2 response. Immunology 108, 230-237 (2003).
54. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell Type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645-1651 (2002).
55. + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742 (1997).
56. + T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production. Eur. J. Immunol. 30, 2344-2354 (2000).
57. Barrat FJ, Cua DJ, Boonstra A et al. In vitro generation of interleukin-10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper Type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med. 195, 603-616 (2002).
58. Vieira PL, Christensen JR, Minaee S et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 172, 5986-5993 (2004).
59. + T cells is induced by immunosuppressive drugs and inhibited by Th1- and Th2-inducing cytokines. Immunol. Lett. 85, 135-139 (2003).
60. + cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421, 388-392 (2003).
61. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Ann. Rev. Immunol. 19, 683-765 (2001).
62. + Regulatory T cells for immunologic self-tolerance and negative control of immune responses. Ann. Rev. Immunol. 22, 531-562 (2004).
63. Weiner HL. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol. Rev. 182, 207-214 (2001).
64. Bennett CL, Christie J, Ramsdell F et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genet. 27, 20-21 (2001).
65. Schubert LA, Jeffery E, Zhang Y, Ramsdell F, Ziegler SF. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 276, 37672-37679 (2001).
66. + regulatory T cells. Nature Immunol. 4, 330-336 (2003).
67. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061 (2003).
68. + T cell effector function.J. Immunol. 171, 1216-1223 (2003).
69. + regulatory T cells in human thymus. Nature 436, 1181-1185 (2005).
70. - T cells. J Clin. Invest. 112, 1437-1443 (2003).
71. Lin W, Truong N, Grossman WJ et al. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J. Allergy Clin. Immunol. 116, 1106-1115 (2005).
72. Ochs HD, Ziegler SF, Torgerson TR. Foxp3 acts as a rheostat of the immune response. Immunol. Rev. 203, 156-164 (2005).
73. Turcanu V, Maleki SJ, Lack G. Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J. Clin. Invest. 111, 1065-1072 (2003).
74. Umetsu DT, Akbari O, Dekruyff RH. Regulatory T cells control the development of allergic disease and asthma. J Allergy Clin. Immunol. 112, 480-487; quiz 488 (2003).
75. Romagnani S. Immunologic influences on allergy and the Th1/Th2 balance. J Allergy Clin. Immunol. 113, 395-400 (2004).
76. Robinson DS, Larche M, Durham SR. Tregs and allergic disease. J. Clin. Invest. 114, 1389-1397 (2004).
77. Akbari O, Dekruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nature Immunol. 2, 725-731 (2001).
78. Hadeiba H, Locksley RM. Lung CD25 CD4 regulatory T cells suppress Type 2 immune responses but not bronchial hyperreactivity. J. Immunol. 170, 5502-5510 (2003).
79. Zuany-Amorim C, Sawicka E, Manlius C et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nature Med. 8, 625-629 (2002).
80. + regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886 (2003).
81. + regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363, 608-615 (2004).
82. Li-Weber M, Davydov I, Krafft H, Krammer P. The role of NF-Y and IRF-2 in the regulation of human IL-4 gene expression. J. Immunol. 153, 4122-4133 (1994).
83. Lee RL, Fields PE, Flavell RA. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447-459 (2001).
84. Tykocinski LO, Hajkova P, Chang HD et al. A critical control element for interleukin-4 memory expression in T helper lymphocytes. J. Biol. Chem. 280, 28177-28185 (2005).
85. Zhang DH, Cohn L, Ray P, Bottomly K, Ray A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272, 21597-21603 (1997).
86. Kaplan MH, Schindler U, Smiley ST, Grusby MJ. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4, 313-319 (1996).
87. Peng SL, Gerth AJ, Ranger AM, Glimcher LH. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity 14, 13-20 (2001).
88. Ho AM, Jain J, Rao A, Hogan PG. Expression of the transcription factor NFATp in a neuronal cell line and in the murine nervous system. J. Biol. Chem. 269, 28181-28186 (1994).
89. Li B, Tournier C, Davis RJ, Flavell RA. Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation. Embo. J. 18, 420-432 (1999).
90. + T cells. Immunity 11, 399-409 (1999).
91. Marsland BJ, Soos TJ, Spath G, Littman DR, Kopf M. Protein kinase C τ is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. J. Exp. Med. 200, 181-189 (2004).
92. Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J. Clin. Invest. 104, 985-993 (1999).
93. Ting CN, Olson MC, Barton KP, Leiden JM. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384, 474-478 (1996).
94. Zhu J, Min B, Hu-Li J et al. Conditional deletion of Gata3 shows its essential function in Th1-Th2 responses. Nature Immunol. 5, 1157-1165 (2004).
95. Yamashita M, Ukai-Tadenuma M, Kimura M et al. Identification of a conserved GATA3 response element upstream proximal of the IL-13 gene locus. J. Biol. Chem. 29, 29 (2002).
96. Yamashita M, Ukai-Tadenuma M, Miyamoto T et al. Essential role of GATA3 for the maintenance of Th2 cytokine production and chromatin remodeling at the Th2 cytokine gene loci. J. Biol. Chem. 279(26), 26983-26990 (2004).
97. Zhang DH, Yang L, Cohn L et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11, 473-482 (1999).
98. Nakamura Y, Ghaffar O, Olivenstein R et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J. Allergy Clin. Immunol. 103, 215-222 (1999).
99. Nakamura Y, Christodoulopoulos P, Cameron L et al. Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge. J. Allergy Clin. Immunol. 105, 1146-1152 (2000).
100. Arakawa S, Hatano Y, Katagiri K. Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis. Clin. Exp. Immunol. 135, 505-510 (2004).
101. Caramori G, Lim S, Ito K et al. Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies. Eur. Respir. J. 18, 466-473 (2001).
102. Pykalainen M, Kinos R, Valkonen S et al. Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. J. Allergy Clin. Immunol. 115, 80-87 (2005).
103. Georas S, Cumberland J, Burke T, Chen R, Schindler U, Casolaro V. Stat6 inhibits interleukin-4 promoter activity in T cells. Blood 92, 4529-4538 (1998).
104. Dorado B, Jerez MJ, Flores N, Martin-Saavedra FM, Duran C, Ballester S. Autocrine IL-4 gene regulation at late phases of TCR activation in differentiated Th2 cells. J. Immunol. 169, 3030-3037 (2002).
105. Lee DU, Rao A. Molecular analysis of a locus control region in the T helper 2 cytokine gene cluster: a target for STAT6 but not GATA3. Proc. Natl Acad. Sci. USA 101, 16010-16015 (2004).
106. Zhu J, Guo L, Min B et al. Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16, 733-744 (2002).
107. Kurata H, Lee HJ, O'Garra A, Arai N. Ectopic expression of activated Stat6 induces the expression of Th2- specific cytokines and transcription factors in developing Th1 cells. Immunity 11, 677-688 (1999).
108. Kuperman D, Schofield B, Wills-Karp M, Grusby MJ. Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production. J. Exp. Med. 187, 939-948 (1998).
109. Yagi R, Nagai H, Iigo Y, Akimoto T, Arai T, Kubo M. Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice. J. Immunol. 168, 2020-2027 (2002).
110. Christodoulopoulos P, Cameron L, Nakamura Y et al. Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J. Allergy Clin. Immunol. 107, 586-591 (2001).
111. Ghaffar O, Christodoulopoulos P, Lamkhioued B et al. In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids. Clin. Exp. Allergy 30, 86-93 (2000).
112. Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP. Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. Clin. Exp. Allergy 34, 1690-1700 (2004).
113. Tamura K, Arakawa H, Suzuki M et al. Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases. Clin. Exp. Allergy 31, 1509-1514 (2001).
114. Duetsch G, Illig T, Loesgen S et al. STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study. Hum. Mol. Genet. 11, 613-621 (2002).
115. Macian F. NFAT proteins: key regulators of T-cell development and function. Nature Rev. Immunol. 5, 472-484 (2005).
116. Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17, 2205-2232 (2003).
117. +, calcineurin, and NFAT. Cell 96, 611-614 (1999).
118. Seminario CS, Burke T, Bochner B, Georas S. Detection of an NFAT-like protein in human eosinophils. Am. J. Respir. Crit. Care Med. 155, A58 (1997).
119. Reddy SP, Mossman BT. Role and regulation of activator protein-1 in toxicant-induced responses of the lung. Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1161-L1178 (2002).
120. Ogawa K, Kaminuma O, Okudaira H et al. Transcriptional regulation of the IL-5 gene in peripheral T cells of asthmatic patients. Clin. Exp. Immunol. 130, 475-483 (2002).
121. Ho IC, Hodge MR, Rooney JW, Glimcher LH. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973-983 (1996).
122. Ho IC, Lo D, Glimcher LH. c-maf promotes T helper cell Type 2 (Th2) and attenuates Th1 differentiation by both interleukin-4-dependent and -independent mechanisms. J. Exp. Med. 188, 1859-1866 (1998).
123. Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH. NF-AT-Driven interleukin-4 transcription potentiated by NIP45. Science 274, 1903-1905 (1996).
124. Kim JI, Ho IC, Grusby MJ, Glimcher LH. The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 10, 745-751 (1999).
125. Cousins DJ, Lee TH, Staynov DZ. Cytokine coexpression during human Th1/ Th2 cell differentiation: direct evidence for coordinated expression of Th2 cytokines. J. Immunol. 169, 2498-2506 (2002).
126. Li-Weber M, Salgame P, Hu C et al. Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter. J. Immunol. 161, 1380-1389 (1998).
127. Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nature Immunol. 4, 616-623 (2003).
128. Agarwal S, Rao A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765-775 (1998).
129. Solymar DC, Agarwal S, Bassing CH, Alt FW, Rao A. A 3′ enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells. Immunity 17, 41-50 (2002).
130. Wang Y, Fischle W, Cheung W, Jacobs S, Khorasanizadeh S, Allis CD. Beyond the double helix: writing and reading the histone code. Novartis Found Symp. 259, 3-17; discussion 17-21, 163-169 (2004).
131. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21 (2002).
132. Valapour M, Guo J, Schroeder JT et al. Histone deacetylation inhibits IL4 gene expression in T cells. J. Allergy Clin. Immunol. 109, 238-245 (2002).
133. Fields PE, Kim ST, Flavell RA. Cutting edge: changes in histone acetylation at the IL-4 and IFN-γ loci accompany Th1/Th2 differentiation. J. Immunol. 169, 647-650 (2002).
134. Makar KW, Perez-Melgosa M, Shnyreva M, Weaver WM, Fitzpatrick DR, Wilson CB. Active recruitment of DNA methyltransferases regulates interleukin-4 in thymocytes and T cells. Nature Immunol. 4, 1183-1190 (2003).
135. Santangelo S, Cousins DJ, Winkelmann NE, Staynov DZ. DNA methylation changes at human Th2 cytokine genes coincide with DNase I hypersensitive site formation during CD4+ T cell differentiation. J. Immunol. 169, 1893-1903 (2002).
136. Lee DU, Agarwal S, Rao A. Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16, 649-660 (2002).
137. Ansel KM, Greenwald RJ, Agarwal S et al. Deletion of a conserved IL-4 silencer impairs T helper Type 1-mediated immunity. Nature Immunol. 5, 1251-1259 (2004).
138. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669 (2000).
139. Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. Distinct effects of T-bet in Th1 lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science 295, 338-342 (2002).
140. + T cells. Nature Immunol. 3, 549-557 (2002).
141. Mullen AC, High FA, Hutchins AS et al. Role of T-bet in commitment of Th1 cells before IL-12-dependent selection. Science 292, 1907-1910 (2001).
142. Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307, 430-433 (2005).
143. Finotto S, De Sanctis GT, Lehr HA et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J. Exp. Med. 193, 1247-1260 (2001).
144. Breuer K, Wittmann M, Kempe K et al. Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper Type 1 response in atopic dermatitis. Clin. Exp. Allergy 35, 1088-1095 (2005).
145. Tantisira KG, Hwang ES, Raby BA et al. TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc. Natl Acad. Sci. USA 101, 18099-18104 (2004).
146. Raby BA, Hwang ES, Van Steen K et al. T-bet polymorphisms are associated with asthma and airway hyperresponsiveness. Am. J. Respir. Crit. Care Med. 173(1), 64-70 (2006).
147. Lambrecht BN, Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nature Rev. Immunol. 3, 994-1003 (2003).
148. Vermaelen K, Pauwels R. Pulmonary dendritic cells. Am. J. Respir. Crit. Care Med. 172, 530-551 (2005).
149. Holt PG, Haining S, Nelson DJ, Sedgwick JD. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol. 153, 256-261 (1994).
150. McWilliam AS, Nelson D, Thomas JA, Holt PG. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J. Exp. Med. 179, 1331-1336 (1994).
151. Hawiger D, Inaba K, Dorsett Y et al. Dendritic cells induce peripheral T cell unresponsiveness under steady-state conditions in vivo. J. Exp. Med. 194, 769-779 (2001).
152. Steinman RM, Nussenzweig MC. Inaugural article: avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA 99, 351-358 (2002).
153. Takeda K, Kaisho T, Akira S. Toll-like receptors. Ann. Rev. Immunol. 21, 335-376 (2003).
154. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430, 257-263 (2004).
155. Caux C, Massacrier C, Vanbervliet B et al. Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 180, 1263-1272 (1994).
156. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184, 747-752 (1996).
157. MacDonald AS, Straw AD, Dalton NM, Pearce EJ. Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J. Immunol. 168, 537-540 (2002).
158. Rissoan MC, Soumelis V, Kadowaki N et al. Reciprocal contort of T helper cell and dendritic cell differentiation [see comments]. Science 283, 1183-1186 (1999).
159. Turley SJ, Inaba K, Garrett WS et al. Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288, 522-527 (2000).
160. Caux C, Vanbervliet B, Massacrier C et al. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J. Exp. Med. 180, 1841-1847 (1994).
161. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of Th1, Th2 and nonpolarized T cells. Nature Immunol. 1, 311-316 (2000).
162. Ebner S, Ratzinger G, Krosbacher B et al. Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4. J. Immunol. 166, 633-641 (2001).
163. + T cell-mediated suppression by dendritic cells. Science 299, 1033-1036 (2003).
164. Lanzavecchia A, Sallusto F. Antigen decoding by T lymphocytes: from synapses to fate determination. Nature Immunol. 2, 487-492 (2001).
165. Lanzavecchia A, Sallusto F. The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr. Opin. Immunol. 13, 291-298 (2001).
166. Huang Q, Liu D, Majewski P et al. The plasticity of dendritic cell responses to pathogens and their components. Science 294, 870-875 (2001).
167. Ronnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J. Exp. Med. 194, F59-F63 (2001).
168. Gilliet M, Boonstra A, Paturel C et al. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195, 953-958 (2002).
169. Blomberg S, Eloranta ML, Magnusson M, Alm GV, Ronnblom L. Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus. Arthritis Rheum. 48, 2524-2532 (2003).
170. Diebold SS, Montoya M, Unger H et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424, 324-328 (2003).
171. Asselin-Paturel C, Boonstra A, Dalod M et al. Mouse Type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nature Immunol. 2, 1144-1150 (2001).
172. Ronnblom L, Eloranta ML, Alm GV. Role of natural interferon-alpha producing cells (plasmacytoid dendritic cells) in autoimmunity. Autoimmunity 36, 463-472 (2003).
173. Boonstra A, Asselin-Paturel C, Gilliet M et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper Type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J. Exp. Med. 197, 101-109 (2003).
174. Charbonnier AS, Hammad H, Gosset P et al. Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response. J. Leukoc. Biol. 73, 91-99 (2003).
175. Kuipers H, Hijdra D, De Vries VC et al. Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells. J. Immunol. 171, 3645-3654 (2003).
176. Redecke V, Hacker H, Datta SK et al. Cutting edge: activation of toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J. Immunol. 172, 2739-2743 (2004).
177. Traidl-Hoffmann C, Mariani V, Hochrein H et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper Type 2 cell polarization. J. Exp. Med. 201, 627-636 (2005).
178. Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote Type 2 cytokine production in maturing human naive T helper cells. J. Immunol. 159, 28-35 (1997).
179. Boldogh I, Bacsi A, Choudhury BK et al. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J. Clin. Invest. 115, 2169-2179 (2005).
180. Ranganath S, Murphy KM. Structure and specificity of GATA proteins in Th2 development. Mol. Cell Biol. 21, 2716-2725 (2001).